Information on EC 2.4.1.B62 - small GTPase glucosyltransferase and Organism(s) Paeniclostridium sordellii and UniProt Accession Q46342

for references in articles please use BRENDA:EC2.4.1.B62
preliminary BRENDA-supplied EC number
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EC Tree
     2 Transferases
         2.4 Glycosyltransferases
             2.4.1 Hexosyltransferases
                2.4.1.B62 small GTPase glucosyltransferase
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Select one or more organisms in this record: ?
This record set is specific for:
Paeniclostridium sordellii
UNIPROT: Q46342 not found.
Word Map
The taxonomic range for the selected organisms is: Paeniclostridium sordellii
The enzyme appears in selected viruses and cellular organisms
Reaction Schemes
+
a small GTPase
=
+
D-glucosyl-[a small GTPase]
Synonyms
Clostridium sordellii lethal toxin, cytotoxin B, cytotoxin L, glucosyltransferase TcdA, glucosyltransferase TcdB, haemorrhagic toxin, hemorrhagic toxin, letal toxin, lethal toxin, lethal-toxin, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Clostridium sordellii lethal toxin
300789
-
haemorrhagic toxin
304533
-
hemorrhagic toxin
304533
-
letal toxin
304534
-
lethal toxin
300789
-
lethal-toxin
300789
-
SYSTEMATIC NAME
IUBMB Comments
UDP-alpha-D-glucose:small GTPase glucosyltransferase
-
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
UDP-alpha-D-glucose + a small GTPase
UDP + D-glucosyl-[a small GTPase]
show the reaction diagram
UDP-alpha-D-glucose + H-Ras
UDP + D-glucosyl-H-Ras
show the reaction diagram
UDP-alpha-D-glucose + human Ras-GTPase
UDP + D-glucosyl-[human Ras-GTPase]
show the reaction diagram
activity of toxin TcsL in human epithelial colorectal adenocarcinoma Caco-2 cells
-
-
?
UDP-alpha-D-glucose + Rac GTPase
UDP + D-glucosyl-[Rac GTPase]
show the reaction diagram
murine host substrate
-
-
?
UDP-alpha-D-glucose + Rac1
UDP + D-glucosyl-Rac1
show the reaction diagram
Rac is the exclusive substrate of the Rho subfamily of GTPases. Rac is a better substrate in the GTDP-bound form than in the GTP-bound form
-
-
?
UDP-alpha-D-glucose + Rac1 GTPase
UDP + D-glucosyl-[Rac1 GTPase]
show the reaction diagram
murine host substrate
-
-
?
UDP-alpha-D-glucose + Ral GTPase
UDP + D-glucosyl-[Ral GTPase]
show the reaction diagram
murine host substrate
-
-
?
UDP-alpha-D-glucose + Rap GTPase
UDP + D-glucosyl-[Rap GTPase]
show the reaction diagram
murine host substrate
-
-
?
UDP-alpha-D-glucose + Ras GTPase
UDP + D-glucosyl-[Ras GTPase]
show the reaction diagram
murine host substrate
-
-
?
UDP-N-acetyl-alpha-D-glucosamine + H-Ras
UDP + N-acetyl-alpha-D-glucosamine-H-Ras
show the reaction diagram
no substrate for wild-type, but substrate for mutant I383S/Q385A
-
-
?
UDP-alpha-D-glucose + a small GTPase
UDP + D-glucosyl-[a small GTPase]
show the reaction diagram
-
-
-
?
UDP-alpha-D-glucose + Cdc42
UDP + D-glucosyl-Cdc42
show the reaction diagram
-
-
-
?
UDP-alpha-D-glucose + H-Ras
UDP + D-glucosyl-H-Ras
show the reaction diagram
good substrate
-
-
?
UDP-alpha-D-glucose + K-Ras
UDP + D-glucosyl-K-Ras
show the reaction diagram
good substrate
-
-
?
UDP-alpha-D-glucose + N-Ras
UDP + D-glucosyl-N-Ras
show the reaction diagram
good substrate
-
-
?
UDP-alpha-D-glucose + Rac1
UDP + D-glucosyl-Rac1
show the reaction diagram
very good substrate
-
-
?
UDP-alpha-D-glucose + RalC
UDP + D-glucosyl-RalC
show the reaction diagram
good substrate
-
-
?
UDP-alpha-D-glucose + Rap2A
UDP + D-glucosyl-Rap2A
show the reaction diagram
good substrate
-
-
?
UDP-alpha-D-glucose + RhoA
UDP + D-glucosyl-RhoA
show the reaction diagram
-
-
-
?
UDP-alpha-D-glucose + RhoB
UDP + D-glucosyl-Rhob
show the reaction diagram
-
-
-
?
UDP-alpha-D-glucose + RhoC
UDP + D-glucosyl-RhoC
show the reaction diagram
-
-
-
?
UDP-alpha-D-glucose + RhoG
UDP + D-glucosyl-RhoG
show the reaction diagram
-
-
-
?
UDP-alpha-D-glucose + TC10
UDP + D-glucosyl-TC10
show the reaction diagram
good substrate
-
-
?
UDP-alpha-D-glucose + TCL signaling G protein
UDP + D-glucosyl-TCL signaling G protein
show the reaction diagram
good substrate
-
-
?
additional information
?
-
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
UDP-alpha-D-glucose + a small GTPase
UDP + D-glucosyl-[a small GTPase]
show the reaction diagram
UDP-alpha-D-glucose + H-Ras
UDP + D-glucosyl-H-Ras
show the reaction diagram
-
-
-
?
UDP-alpha-D-glucose + human Ras-GTPase
UDP + D-glucosyl-[human Ras-GTPase]
show the reaction diagram
activity of toxin TcsL in human epithelial colorectal adenocarcinoma Caco-2 cells
-
-
?
UDP-alpha-D-glucose + Rac GTPase
UDP + D-glucosyl-[Rac GTPase]
show the reaction diagram
murine host substrate
-
-
?
UDP-alpha-D-glucose + Rac1 GTPase
UDP + D-glucosyl-[Rac1 GTPase]
show the reaction diagram
murine host substrate
-
-
?
UDP-alpha-D-glucose + Ral GTPase
UDP + D-glucosyl-[Ral GTPase]
show the reaction diagram
murine host substrate
-
-
?
UDP-alpha-D-glucose + Rap GTPase
UDP + D-glucosyl-[Rap GTPase]
show the reaction diagram
murine host substrate
-
-
?
UDP-alpha-D-glucose + Ras GTPase
UDP + D-glucosyl-[Ras GTPase]
show the reaction diagram
murine host substrate
-
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Mn2+
stimulation, maximum activity at 1 mM
K+
in addition to divalent cations, costimulation by K+ is required
Mg2+
EC50 value 0.180 mM
Mn2+
EC50 value 0.028 mM
additional information
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
EDTA
2 mM, complete inhibition
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.004
UDP-alpha-D-glucose
mutant S385/A387Q, pH 7.5, 37°C
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.39
UDP-alpha-D-glucose
mutant S385/A387Q, pH 7.5, 37°C
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
91.7
UDP-alpha-D-glucose
mutant S385/A387Q, pH 7.5, 37°C
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
the difference in cellular Rac1 and Ras glucosylation when the autoprocessing activity is ablated (mutation C698A) suggests that there is a localization difference for Rac1 and Ras. Mutations in the GTD membrane localization domain inhibit TcsL cytotoxicity
physiological function
physiological function
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
TCSL1_PAESO
2364
0
270580
Swiss-Prot
-
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
63992
x * 63992, catalytic fragment, residues 1-546
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
?
x * 63992, catalytic fragment, residues 1-546
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
proteolytic modification
maturation of the host cell endosome causes a conformational change in the pore-forming domain of TcsL, causing it to form a pore in the endosomal membrane. The autoprocessing domain is activated by host inositol hexakisphosphate and cleaves the glucosyltransferase domain (GTD), presumably to permit access to substrates residing at the plasma membrane
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
catalytic fragment, residues 1-546, to 2.3 A resolution. Geometry suggests that the reaction runs as a circular electron transfer in a six-membered ring, which involves the deprotonation of the nucleophile by the beta-phosphoryl group of the donor substrate UDP-glucose
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
C698A
site-directed mutagenesis of the autoprocessing domain, mutant TcsL C698A is able to quickly glucosylate Rac1, similar to wild-type TcsL, but is attenuated in its ability to glucosylate Ras GTPases. The introduction of the autoprocessing mutation does not impact the glucosylation of Rac1 or H-Ras in an in vitro assay
F17N/R18A
site-directed mutagenesis in the GTD membrane localization domain, on the surface of the membrane localization domain (MLD), the mutant shows a defect in membrane association in a liposome binding assay
F17N/R18A/C698A
site-directed mutagenesis in the GTD membrane localization domain, on the surface of the membrane localization domain (MLD), the mutant shows a defect in membrane association in a liposome binding assay. The triple mutant is also inhibited in both Rac1 and Ras glucosylation
I383S/Q385A
mutation allow modification of Ras in the presence of UDP-N-acetyl-glucosamine and reduces the acceptance of UDP-glucose as a donor for glycosylation
F17K
mutation strongly decreases binding to brain phosphatidylserine
K11I
mutation moderately decreases binding to brain phosphatidylserine
K16I
mutation moderately decreases binding to brain phosphatidylserine
Q10A
mutation does not significantly decrease binding to brain phosphatidylserine
Q20A
mutation moderately decreases binding to brain phosphatidylserine
R18P
mutation strongly decreases binding to brain phosphatidylserine
R68A
mutation strongly decreases binding to brain phosphatidylserine
S38A
mutation does not significantly decrease binding to brain phosphatidylserine
V15S
mutation strongly decreases binding to brain phosphatidylserine
Y14A
mutation strongly decreases binding to brain phosphatidylserine
Y78A
mutation does not significantly decrease binding to brain phosphatidylserine
additional information
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant His6-tagged wild-type and mutant enzymes from Bacillus megaterium by nickel affinity chromatography and gel filtration
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expression of catalytic fragment, residues 1-546
gene tcsL, recombinant expression of His6-tagged wild-type and mutant enzymes in Bacillus megaterium
expression in Escherichia coli
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Just, I.; Selzer, J.; Hofmann, F.; Green, G. A.; Aktories, K.
Inactivation of Ras by Clostridium sordellii lethal toxin-catalyzed glucosylation
J. Biol. Chem.
271
10149-10153
1996
Paeniclostridium sordellii (Q46342), Paeniclostridium sordellii 6018 (Q46342)
Manually annotated by BRENDA team
Jank, T.; Reinert, D.; Giesemann, T.; Schulz, G.; Aktories, K.
Change of the donor substrate specificity of Clostridium difficile toxin B by site-directed mutagenesis
J. Biol. Chem.
280
37833-37838
2005
Clostridioides difficile (P18177), Clostridioides difficile, Clostridium novyi (Q46149), Clostridium novyi, Paeniclostridium sordellii (Q46342), Paeniclostridium sordellii, Paeniclostridium sordellii 6018 (Q46342), Clostridium novyi 19402 (Q46149), Clostridioides difficile VPI 10463 (P18177)
Manually annotated by BRENDA team
Ziegler, M.O.; Jank, T.; Aktories, K.; Schulz, G.E.
Conformational changes and reaction of clostridial glycosylating toxins
J. Mol. Biol.
377
1346-1356
2007
Clostridium novyi (Q46149), Paeniclostridium sordellii (Q46342)
Manually annotated by BRENDA team
Genth, H.; Pauillac, S.; Schelle, I.; Bouvet, P.; Bouchier, C.; Varela-Chavez, C.; Just, I.; Popoff, M.R.
Haemorrhagic toxin and lethal toxin from Clostridium sordellii strain vpi9048: molecular characterization and comparative analysis of substrate specificity of the large clostridial glucosylating toxins
Cell. Microbiol.
16
1706-1721
2014
Paeniclostridium sordellii (M9ZTT7), Paeniclostridium sordellii (V5T923), Paeniclostridium sordellii, Paeniclostridium sordellii vpi9048 (M9ZTT7), Paeniclostridium sordellii vpi9048 (V5T923)
Manually annotated by BRENDA team
Varela Chavez, C.; Hoos, S.; Haustant, G.M.; Chenal, A.; England, P.; Blondel, A.; Pauillac, S.; Lacy, D.B.; Popoff, M.R.
The catalytic domains of Clostridium sordellii lethal toxin and related large clostridial glucosylating toxins specifically recognize the negatively charged phospholipids phosphatidylserine and phosphatidic acid
Cell. Microbiol.
17
1477-1493
2015
Paeniclostridium sordellii (V5T923), Paeniclostridium sordellii
Manually annotated by BRENDA team
Varela Chavez, C.; Haustant, G.M.; Baron, B.; England, P.; Chenal, A.; Pauillac, S.; Blondel, A.; Popoff, M.R.
The tip of the four N-terminal alpha-helices of Clostridium sordellii lethal toxin contains the interaction site with membrane phosphatidylserine facilitating small GTPases glucosylation
Toxins
8
90
2016
Paeniclostridium sordellii (V5T923), Paeniclostridium sordellii
Manually annotated by BRENDA team
Thiele, T.L.; Stuber, T.P.; Hauer, P.J.
Detection of Clostridium sordellii strains expressing hemorrhagic toxin (TcsH) and implications for diagnostics and regulation of veterinary vaccines
Vaccine
31
5082-5087
2013
Paeniclostridium sordellii (M9ZTT7), Paeniclostridium sordellii (V5T923), Paeniclostridium sordellii, Paeniclostridium sordellii VPI 9048 (M9ZTT7), Paeniclostridium sordellii VPI 9048 (V5T923)
Manually annotated by BRENDA team
Genth, H.; Schelle, I.; Just, I.
Metal ion activation of Clostridium sordellii lethal toxin and Clostridium difficile toxin B
Toxins
8
109
2016
Clostridioides difficile (P18177), Clostridioides difficile, Paeniclostridium sordellii (V5T923), Paeniclostridium sordellii
Manually annotated by BRENDA team
Genth, H.; Junemann, J.; Laemmerhirt, C.M.; Luecke, A.C.; Schelle, I.; Just, I.; Gerhard, R.; Pich, A.
Difference in mono-O-glucosylation of Ras subtype GTPases between toxin A and toxin B from Clostridioides difficile strain 10463 and lethal toxin from Clostridium sordellii strain 6018
Front. Microbiol.
9
3078
2018
Clostridioides difficile (P16154), Clostridioides difficile (P18177), Clostridioides difficile, Paeniclostridium sordellii (Q46342), Paeniclostridium sordellii, Paeniclostridium sordellii 6018 (Q46342), Clostridioides difficile 10463 (P16154), Clostridioides difficile 10463 (P18177)
Manually annotated by BRENDA team
Craven, R.; Lacy, D.
Clostridium sordellii lethal-toxin autoprocessing and membrane localization activities drive GTPase glucosylation profiles in endothelial cells
mSphere
1
e00012-15
2016
Paeniclostridium sordellii (Q46342), Paeniclostridium sordellii, Paeniclostridium sordellii JGS6382 (Q46342)
Manually annotated by BRENDA team
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